Process for the preparation of 2-acylamino-6-halopurine from 2,9-diacylguanine

Abstract

2-Acylamino-6-halopurine can be prepared by halogenation of 2,9-diacylguanine (2-acylamino-6-oxo-9-acylpurine) with phosphorus oxychloride or phosphorus oxybromide in the presence of a base and of a salt with subsequent hydrolysis of the reaction product.

I claim: 
     
       1. A process for the preparation of the compound of the formula I ##STR4## in which R 1  is a straight-chain or branched acyl group having 2 to 10 carbon atoms or an aroyl group having 7 to 10 carbon atoms and X is chlorine or bromine, which comprises reacting 2,9-diacylguanine of the formula II ##STR5## in which R 1  and R 2 , which can be the same or different, are a straight-chain or branched acyl group having 2 to 10 carbon atoms or an aroyl group having 7 to 10 carbon atoms, with a halogenating agent in the presence of a base and of a salt and hydrolyzing the reaction product. 
     
     
       2. The process as claimed in claim 1, wherein phosphorus oxychloride or phosphorus oxybromide is used as the halogenating agent. 
     
     
       3. The process as claimed in claim 1, wherein N,N-dimethylaniline, N-ethylpiperidine or triethylamine is used as a base and triethylamine hydrochloride, tetrabutylammonium chloride, tetraethylammonium bromide, tetramethylammonium chloride, tetramethylammonium bromide, tetrabutylammonium bromide or tetraethylammonium chloride is used as a salt. 
     
     
       4. The process as claimed in claim 1, wherein the reaction is carried out at a temperature between -10° C. and 80° C. 
     
     
       5. The process as claimed in claim 1, wherein the molar ratio of halogenating agent to the compound of the formula II is 1-10 to 1. 
     
     
       6. The process as claimed in claim 5, wherein the molar ratio is 4-6 to 1. 
     
     
       7. The process as claimed in claim 1, wherein the molar ratio of salt to the compound of the formula II is 1-3 to 1. 
     
     
       8. The process as claimed in claim 1, wherein the molar ratio of base to the compound of the formula II is 1-6 to 1. 
     
     
       9. The process as claimed in claim 1, wherein the hydrolysis is carried out at a pH between 3 and 8. 
     
     
       10. The process as claimed in claim 9, wherein the hydrolysis is carried out at a temperature between -10° C. and 30° C.